20MO Time to deterioration in quality of life in patients (pts) with advanced endometrial cancer (aEC) treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC)

BackgroundIn study 309/KEYNOTE-775, L+P showed significant OS and PFS benefits and improved ORR vs TPC in pts with aEC following prior platinum-based therapy. There were no substantial differences in health-related quality of life (HRQoL) scores between the 2 arms at 12 weeks. We describe a post-hoc analysis of time to first (TTfD) and time to definitive (TTdD) deterioration (by 10 points) of patient-reported outcomes (PROs).MethodsPts were randomized 1:1 to lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW, 3 wks on/1 wk off). PROs were assessed on day 1 of each treatment cycle (L+P and doxorubicin, 21 days; paclitaxel, 28 days) until the end of treatment visit using EORTC QLQ-C30, QLQ-EN24, and EQ-5D-5L in pts with ≥1 study dose and ≥1 postbaseline PRO. TTfD for the EORTC QLQ-C30 and QLQ-EN24 was defined as the time from treatment start to first onset of a ≥10-point increase (symptom score) or decrease (functional/global health status [GHS] score) from baseline. TTdD was defined as the time from treatment start to first onset of an increase (symptom score) or decrease (functional/GHS score) of ≥10 points from baseline without subsequent recovery.ResultsThe mean observation period for PRO measures was longer for L+P vs TPC (eg, EORTC QLQ-C30: L+P, 9.3 mos; TPC, 4.3 mos). TTfD was generally similar between the 2 arms for most functional scales. Among the symptom scales, TTfD for dyspnea, poor body image, tingling/numbness, and hair loss favored L+P over TPC, whereas pain, appetite loss, diarrhea, and muscular pain favored TPC. TTdD favored L+P for most of the assessed scales.ConclusionsAlthough TTfD did not demonstrably favor either arm, L+P was favored over TPC for almost all scales in the TTdD analysis. This may be due to longer follow-up and/or overall greater efficacy with L+P vs TPC. These data along with previously reported positive efficacy, safety, and overall HRQoL scores from Study 309/KEYNOTE-775 further support L+P for use in pts with aEC following prior platinum-based therapy.Clinical trial identificationNCT03517449.Editorial acknowledgementMedical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Legal entity responsible for the studyEisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.FundingEisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.DisclosureD. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: MSD; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: Clovis Oncology; Financial Interests, Personal, Other, Consultancy: PharmaMar; Financial Interests, Personal, Other, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Clovis Oncology; Financial Interests, Personal, Other, Consultancy: GSK; Financial Interests, Personal, Other, Consultancy: MSD; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Other, Consultancy: Immunogen; Financial Interests, Personal, Other, Consultancy: Genmab; Financial Interests, Personal, Other, Consultancy: Seagen; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Seagen; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Genmab; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Oncoinvest; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Corcept; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Sutro; Financial Interests, Institutional, Funding, Grant for Founding Academic Trial: MSD; Financial Interests, Institutional, Funding, Grant for Founding Academic Trial: Clovis Oncology; Financial Interests, Institutional, Funding, Grant for Founding Academic Trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT Trial with Institutional Support for Coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT Trial with Institutional Support for Coordination: Genmab; Financial Interests, Institutional, Funding, Grant for founding academic trial: PharmaMar; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca; Financial Interests, Institutional, Funding, Clinical trial/contracted research: Clovis Oncology; Financial Interests, Institutional, Funding, Clinical trial/contracted research: GSK; Financial Interests, Institutional, Funding, Clinical trial/contracted research: MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Immunogen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Incyte; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Novartis; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Roche; Financial Interests, Institutional, Invited Speaker, ENGOT Trial with Institutional Support for Coordination: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: Genmab; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Immunogen; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Clovis; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Incyte; Non-Financial Interests, Personal, Member, Board of Directors: GCIG. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche; Financial Interests, Personal, Advisory Board, Various: PharmaMar; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, Various: AstraZeneca; Financial Interests, Personal, Advisory Board, Various: MSD/Merck; Financial Interests, Personal, Advisory Board, Various: Clovis Oncology; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: Tesaro; Financial Interests, Personal, Advisory Board, Various: Tesaro; Financial Interests, Personal, Advisory Board, Various: GSK; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Various: Pfizer; Financial Interests, Personal, Advisory Board, Various: Takeda; Financial Interests, Personal, Advisory Board, Various: BIOCAD; Financial Interests, Personal, Advisory Board, Various: Immunogen; Financial Interests, Personal, Advisory Board, Various: Mersana; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Personal, Advisory Board, Advisory role: Pieris; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Personal, Other, Steering Committee Member Clinical Guidelines: ESMO; Non-Financial Interests, Personal, Leadership Role, Chair, Scientific Committee: ACTO (Alleanza Contro il Tumore Ovarico). A. Casado Herraez: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: PharmaMar; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Lilly; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: PharmaMar; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche. A.D. Santin: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Institutional, Funding: Tesaro; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Gilead Sciences; Financial Interests, Institutional, Funding: Puma Biotechnology; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: R-Pharm; Financial Interests, Institutional, Funding: Immunomedics. E. Colomba: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Travel. Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. D.S. Miller: Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Other, Honoraria: Clovis Oncology; Financial Interests, Personal, Member, Honoraria: Genentech; Financial Interests, Personal, Research Grant: EMD Serono Research & Development Institute; Financial Interests, Institutional, Research Grant: US Biotest; Financial Interests, Institutional, Research Grant: Advenchen Laboratories; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Xenetic Biosciences; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Aeterna Zentaris; Financial Interests, Institutional, Research Grant: TRACON Pharma; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Immunogen; Financial Interests, Institutional, Research Grant: Mateon Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Millennium Pharmaceuticas; Financial Interests, Institutional, Research Grant: Aprea AB; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: NVision; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Syros Pharmaceuticals; Financial Interests, Institutional, Research Grant: Karyopharm Therapeutics; Financial Interests, Institutional, Research Grant: Agenus and Akesobio; Financial Interests, Institutional, Research Grant: Merck Sharpe & Dohme; Financial Interests, Personal, Other, Consulting Fees: Genentech; Financial Interests, Personal, Other, Consulting Fees: Tesaro; Financial Interests, Personal, Other, Consulting Fees: Eisai; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca; Financial Interests, Personal, Other, Consulting Fees: Guardant Health; Financial Interests, Personal, Other, Consulting Fees: Janssen Oncology; Financial Interests, Personal, Other, Consulting Fees: Alexion Pharmaceuticals; Financial Interests, Personal, Other, Consulting Fees: Karyopharm Therapeutics; Financial Interests, Personal, Other, Consulting Fees: Incyte; Financial Interests, Personal, Other, Consulting Fees: Guardant Health; Financial Interests, Personal, Other, Consulting Fees: Janssen; Financial Interests, Personal, Other, Consulting Fees: Clovis Oncology; Financial Interests, Personal, Other, Consulting Fees: Asymmetrics Therapeutics LLC; Financial Interests, Personal, Other, Consulting Fees: Boston Biomedical Research Institute; Financial Interests, Personal, Other, Consulting Fees: Tarveda Therapeutics; Financial Interests, Personal, Other, Consulting Fees: Myriad Genetic Laboratories Inc.; Financial Interests, Personal, Other, Consulting Fees: GlaxoSmithKline LLC; Financial Interests, Personal, Other, Consulting Fees: AbbVie Inc.; Financial Interests, Personal, Other, Consulting Fees: EMD Serono Inc.; Financial Interests, Personal, Other, Consulting Fees: Seager Inc.; Financial Interests, Institutional, Other, Consulting Fees: Merck Sharpe & Dohme. K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: Nano Carrier; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Zeria; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Personal, Invited Speaker: Regenerone; Financial Interests, Personal, Invited Speaker: Zeria; Non-Financial Interests, Personal, Leadership Role: GOTIC. S. Pignata: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: PPharmaMar; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Az. S.E. Baron-Hay: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Merck Sharpe & Dohme; Financial Interests, Personal, Advisory Role: Novartis. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Other, COLIBRI Translational Research: BMS; Financial Interests, Personal, Advisory Board: Oxnea; Financial Interests, Personal, Advisory Board: Merck Sereno; Financial Interests, Personal, Advisory Board: Agenus; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Financial Interests, Personal, Advisory Board: Clovis; Non-Financial Interests, Personal, Principal Investigator: PAOLA1. R. 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Makker: Financial Interests, Institutional, Funding, Study funding: Merck; Financial Interests, Institutional, Funding, Study funding: Eisai; Financial Interests, Institutional, Funding, Study funding: Clovis; Financial Interests, Institutional, Funding, Study funding: Karyopharm; Financial Interests, Institutional, Funding, Study funding: AstraZeneca; Financial Interests, Institutional, Funding, Study support: Zymeworks; Non-Financial Interests, Personal, Principal Investigator: Merck; Non-Financial Interests, Personal, Advisory Role: Eisai; Non-Financial Interests, Personal, Advisory Role: Clovis; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: GSK; Non-Financial Interests, Personal, Advisory Role: Karyopharm; Non-Financial Interests, Personal, Advisory Role: Iteos; Non-Financial Interests, Personal, Advisory Role: Faeth. All other authors have declared no conflicts of interest. BackgroundIn study 309/KEYNOTE-775, L+P showed significant OS and PFS benefits and improved ORR vs TPC in pts with aEC following prior platinum-based therapy. There were no substantial differences in health-related quality of life (HRQoL) scores between the 2 arms at 12 weeks. We describe a post-hoc analysis of time to first (TTfD) and time to definitive (TTdD) deterioration (by 10 points) of patient-reported outcomes (PROs). In study 309/KEYNOTE-775, L+P showed significant OS and PFS benefits and improved ORR vs TPC in pts with aEC following prior platinum-based therapy. There were no substantial differences in health-related quality of life (HRQoL) scores between the 2 arms at 12 weeks. We describe a post-hoc analysis of time to first (TTfD) and time to definitive (TTdD) deterioration (by 10 points) of patient-reported outcomes (PROs). MethodsPts were randomized 1:1 to lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW, 3 wks on/1 wk off). PROs were assessed on day 1 of each treatment cycle (L+P and doxorubicin, 21 days; paclitaxel, 28 days) until the end of treatment visit using EORTC QLQ-C30, QLQ-EN24, and EQ-5D-5L in pts with ≥1 study dose and ≥1 postbaseline PRO. TTfD for the EORTC QLQ-C30 and QLQ-EN24 was defined as the time from treatment start to first onset of a ≥10-point increase (symptom score) or decrease (functional/global health status [GHS] score) from baseline. TTdD was defined as the time from treatment start to first onset of an increase (symptom score) or decrease (functional/GHS score) of ≥10 points from baseline without subsequent recovery. Pts were randomized 1:1 to lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW, 3 wks on/1 wk off). PROs were assessed on day 1 of each treatment cycle (L+P and doxorubicin, 21 days; paclitaxel, 28 days) until the end of treatment visit using EORTC QLQ-C30, QLQ-EN24, and EQ-5D-5L in pts with ≥1 study dose and ≥1 postbaseline PRO. TTfD for the EORTC QLQ-C30 and QLQ-EN24 was defined as the time from treatment start to first onset of a ≥10-point increase (symptom score) or decrease (functional/global health status [GHS] score) from baseline. TTdD was defined as the time from treatment start to first onset of an increase (symptom score) or decrease (functional/GHS score) of ≥10 points from baseline without subsequent recovery. ResultsThe mean observation period for PRO measures was longer for L+P vs TPC (eg, EORTC QLQ-C30: L+P, 9.3 mos; TPC, 4.3 mos). TTfD was generally similar between the 2 arms for most functional scales. Among the symptom scales, TTfD for dyspnea, poor body image, tingling/numbness, and hair loss favored L+P over TPC, whereas pain, appetite loss, diarrhea, and muscular pain favored TPC. TTdD favored L+P for most of the assessed scales. The mean observation period for PRO measures was longer for L+P vs TPC (eg, EORTC QLQ-C30: L+P, 9.3 mos; TPC, 4.3 mos). TTfD was generally similar between the 2 arms for most functional scales. Among the symptom scales, TTfD for dyspnea, poor body image, tingling/numbness, and hair loss favored L+P over TPC, whereas pain, appetite loss, diarrhea, and muscular pain favored TPC. TTdD favored L+P for most of the assessed scales. ConclusionsAlthough TTfD did not demonstrably favor either arm, L+P was favored over TPC for almost all scales in the TTdD analysis. This may be due to longer follow-up and/or overall greater efficacy with L+P vs TPC. These data along with previously reported positive efficacy, safety, and overall HRQoL scores from Study 309/KEYNOTE-775 further support L+P for use in pts with aEC following prior platinum-based therapy. Although TTfD did not demonstrably favor either arm, L+P was favored over TPC for almost all scales in the TTdD analysis. This may be due to longer follow-up and/or overall greater efficacy with L+P vs TPC. These data along with previously reported positive efficacy, safety, and overall HRQoL scores from Study 309/KEYNOTE-775 further support L+P for use in pts with aEC following prior platinum-based therapy.